Project will assess the influence of gradually imposed, adult-initiated controlled dietary restriction on spontaneous cancerogenesis in A. Ca/Sn male mice, an H-2 congenic strain which develops pulmonary tumors and hepatomas. The effect of age at time of initiation of underfeeding will be tested. Individually caged mice consuming since weaning a semi-synthetic diet in amounts which allow "normal" growth will be dietarily restricted at either 5 months or 10 months of age. The diets used will supply the same amounts per week of protein (casein), vitamins and salts to all mice, but calories will be limited for restricted mice such that they will consume 70 percent the amount as controls during the first month of underfeeding, and 55 percent thereafter. These diets produce undernutrition not malnutrition. Dietary influence on the aging immune apparatus will be measured with emphasis on immunologic suppressor effects. Mice will be sacrificed for evaluation of several age-sensitive immune indices at 14-15 and 19-20 months of age. These include: lymphocyte proliferation (alloantigen or mitogen-stimulated tritiated thymidine uptake in vitro; colony growth in soft agar), humoral immune response (plaque forming cell levels to sheep erythrocytes following in vitro sensitization) and lymphocytoxicity (cytolytic response to an allogeneic tumor following in vitro sensitization). Manipulation of these basic assays will reveal the level of suppressor activity which seems to increase in tumor-bearing hosts and with advancing age. Effects of tumor type on these immunologic parameters will also be determined. This study should further define the efficacy of adult-onset dietary restriction as an inhibitor of spontaneous cancerogenesis that was observed in previous studies. The use of improved diets and feeding strategies with an emphasis on the role of immunologic phenomena in this study should help clarify this phenomena.